Product derived from opium and process of making same.



ora ion ALFONS GAMS, 0F IBASEL, SWITZERLAND, ASSIGNOR 'I'O SOCIETY OFCHEMIGAL INDUSTRY'IN BASLE, 0F BASEI, SWITZERLAND.

PRODUCT DERIVED FROM OPI UM AND PROCESS OF MAKING SAME,-

No Drawing.

To all whom it may concern:

Be it known that I, ALFONS GAMS, chemist, a citizen of the SwissRepublic, and resident of Basel, Switzerland, have invented a newProduct Derived from Opium and Process of Making Same, of which thefollowing is a full, clear, and exact specification.

Attempts have already been made to prepare with opium a product solublein water, suitable for injections and possessing the whole unalteredaction of the opium. As is known, neither the opium tincture, nor theopium extract which dissolves to a turbid solution, possess theseproperties, the said opium extract containing by the by only a part ofthetherapeuticallv valuable alkaloids narcotin, papaverinand thebain.

By extracting opium with dilute mineral acids, the natural forms ofcombination of its active substances are destroyed, that is to say themeconates, etc., are decomposed to corresponding salts of the mineralacids and meconic acid and the like are split off. By extracting opiumwith non volatile organic acids, as for instance tartaric acid, it isnecessary to employ an excess of the acid for obtaining a completeextraction; but owing to this want of volatility the said ex cess oforganic acid cannot be removed subsequently, without destroyingsimultaneously the natural forms of combination of the opium alkaloids.By extracting opium with certain volatile organic acids, as for instanceacetic acid, all the active constituents namely the narcotin and thepapaverin are not transformed into stable salts, so that the productsprepared with aid of acetic acid contain only a part oft-he saidvaluable alkaloids. v 1

I have now found, that a product derived from opium which dissolves inwater to a clear solution, is'miitable forinjections and contains allthe opium alkaloids in their natural forms of combination and in theirnatural proportions, can be obtained by extracting from the opium withwater its active constituents constituted-by salts soluble in water, asfor instance the meconates, without destroying their natural forms ofcombination, and by treating the residue remaining after thisextraction, which contains a number of further valuable constitucuts, asnarcotin, papaverin and thebain, in form of bases. with dilute alcoholto which have been added small quantities of formic Specification ofLetters Patent.

are then removed from the dilute alcohohc- Patented Get. 23, rear.

Application filed. March 24 1917. Serial No. 157,215.

solution thus obtained by distillation in a vacuum and the solution isseparated by filtration from the remaining inactive substances. There isthus obtained an aqueous solution of the forinates of the specifiedalkaloids, which is added to the aqneous extract first obtained and themixture is diluted with water to a multipleof its volume, whereby themucilaginous substances and other inactive substances are precipitated."

By evaporating the filtered solution in a vacuum there is directlyobtained a product which contains all the alkaloids in a form soluble inwater, some in their natural forms of combination and the rest in theform of organic acid salts in the same natural quan- I titativeproportions, as they are contained in the natural drug, and which can beemployed directly for injection purposes. In order to eliminate the lastremnants of albuminous substances from the obtained solu-v are extractedtwice in succession with cold water, using 800 com. for each extraction,the two extracts are poured together. The remaining residue is extractedwith a liter of cold alcohol of per cent. strength, to which 1' com. ofconcentrated formic acid has been added. Two solutions, an aqueous oneand a slightly formic dilute alcoholic one, are thus obtained. Thelatter is freed from alcohol by distillation in a, vacuum and ifhereafter the solution contains still some formic acid, this latter iseliminated from the solution by adding water and a further distillation.After the separated resinous and fatty constituents have been eliminatedby convenient filtration, the clear aqueous solution thus. obtained isadded to whereby the new product derived from F solution.

the first aqueous extract which has in the meantime been evaporated in avacuum to a small volume, and the whole solution diluted with distilledwater to a multiple of its volume, whereby mucilaginous substances areprecipitated which can be separated by filtering. The remaining clearsolution is evaporated to dryness in a vacuum,

opium is obtained in the form of a light yellow-brown powder (116 to 120gr.). It dissolves in water to a light brown-yellow Its aqueous solutiongives with Mayers reagent a voluminous precipitate, withphospho-tungstic acid a voluminous beige-colored precipitate, withpicric acid a canary-yellow precipitate and with sodium acetate avoluminous precipitate (papaverin and narcotin). By adding a mineralacid to the aqueous solution and allowing the mixture to stand for acertain time, the mixture becomes gradually red, quicker when heated.

f the aqueous solution be shaken with acetic ether, the separated layerof acetic ether be floated on a little water and a drop of a dilute offerric chlorid solution be added, no red zone is formed even after along standing, showing the absence of free a short time.

meconic acid. The same is the case when the aqueous solution ispreviously boiled for But if a drop of a dilute mineral acid is added tothe aqueous solution, the a plication of the test described above prouces a deep-red zone. showing that the meconic acid has been liberatedby the added mineral acid.

If a further purification of the product obtained by the above specifiedprocess is desired, a dilute aqueous solution of lead salt, as forinstance of lead formate, is added to the dilute aqueous solution,containing a little quantity of formic acid, obtained according to theabove described processfafter separation of the mucilaginous substances;after filtration the lead is removed from the filtered solution by meansof hydrogen sulfid and finally the solution evaporated to dryness. Inthis manner it becomes possible to remove the last traces of albuminoussubstancewhich may have been dissolved in the solution.

What I claim is:

' 1. The herein described process for the manufacture of a productderived from opium, soluble in water, suitable for injecuens andcontaining all the alkaloids in their natural forms of combination andin their natural proportions, consisting in extracting first the opiumwith water, extract ing afterward the remaining residue with di-- #l-utealcohol td which has been added formic acid, which forms stable saltswith narcotin, papaverin and thebain, freeing the 1 solution obtained bythis second extraction from alcohol and from volatile formic acid inexcess and removing therefrom the separated inactive substances, addingthis latter solution to the solution which has beefi obtained by theaqueous extraction,-dili1t-' ing the resulting mixture with water to amultiple of its volume, in order to precipitate t e mucilaginoussubstances, and evapcrating, after filtration, the liquid to dryness ina vacuum. v

2. The herein described process for the manufacture of a product derivedfrom opium, soluble in water, suitable for injections and containing allthe alkaloids in their natural forms of combination and in their naturalproportions, consisting in extracting first the opium with water, eX-tracting afterward the remaining residue with dilute alcohol to whichhas been added formic acid which forms stable salts with narcotin,papaverin and thebain, freeing the solution obtained by this secondextraction from alcohol and from volatile formic acid in excess andremoving therefrom the separated-inactive substances, adding this lattersolution to the solution which has been obtained by the aqueousextraction,

- water, suitable for injections and containing all the alkaloids of theopium in their nat ural forms of combination and in their natural.proportions, constituting a light yellow powder, dissolving in water tolight yellow-brown dissolutions, which gives with Mayers reagent avoluminous precipitate,

with phospliotungstic acid a voluminous beige colored precipitate, withpicric acid a canary yellow precipitate and with sodium acetate avoluminous precipitate, and with mineral acid after standing for a longtime a red coloration which may be obtained more quickly by heating.

In witness whereof Ihave hereunto signed my name this 28th day ofFebruary 1917, in the presence of two subscribing witnesses.

ALFONS GAMS. Witnesses LYDIA llnnnnn, AMAND Rrr'rnn.

